The synthesis of conjugated oligomers with precisely controlled, well-defined conjugation length is valuable for fine tuning of the physical and photo-physical properties of conjugated polymers. A series of oligomers of precisely controlled structure can be used as a model for the investigation of processes governing the physical and photophysical properties of the corresponding larger, polydisperse polymeric materials. Monodisperse conjugated oligomers contain minimal structural defects compared to the polymers, and allow greater control of the material's electronic properties. The synthesis of well-defined oligomers typically requires multi-step approaches utilizing multiple iterations of protection/deprotection chemistry and purification at each step, making such synthesis very low yielding. The development of one-pot synthetic methods towards oligomers with well-defined conjugation length is highly desirable.
Among conjugated polymers (CPs), poly(p-phenyleneethynylene)s (PPEs) are a class of bright, fluorescent materials with excellent physical and photophysical properties and emerging applications in solar cell electronics, fluorescence analyte sensing, imaging, and targeted cellular delivery of therapeutics.
The synthesis of conventional PPEs utilizes the palladium-mediated Sonogashira coupling reaction between aryl halides and terminal alkynes (AABB-type polymerization). The polymerization under these conditions proceeds in a stepwise manner, requires a high degree of stoichiometric balance, and results in an alternating A-B-type polymer, as indicated in Scheme 1, below, typically with a relatively large polydispersity index.

Several approaches to the synthesis of oligo-PPEs have explored different features of the Sonogashira reaction. These include the intentional breaking of stoichiometric balance, differences in reactivity between different aryl halides, Huang et al., Tetrahedron Lett. 1999, 40, 3447-3450, polymer end-group activation, Kovalev et al., Macromol. Chem. Phys. 2005, 206, 2112-2121, and catalyst transfer polycondensation, Kang, et al., J. Am. Chem. Soc. 2013, 135, 4984-4987. More precise control can be achieved by step-by-step or convergent synthesis utilizing a series of protection, coupling and deprotection steps, VanVeller et al., “Poly(aryleneethynylene)s” pages 175-200 in Design and Synthesis of Conjugated Polymers, M. Leclerc, J. Morin (Eds.) Wiley-VCH: Weinheim, 2010. All of the above approaches require multiple purification steps, and are thus time-consuming, low-yielding and costly.
Labeling and monitoring of biological substances and activities in live cells are crucial for understanding complex biological systems, and can permit development of biological/biomedical sensors or therapeutic means for various diseases. Small fluorescent molecules have been used for labeling and sensing of various cellular substances including nucleic acids, proteins, intracellular organelles, whole cells, and tissues. Small molecular weight compounds often use passive diffusion mechanism to enter cells. There are several issues resulting from the high concentrations required to create a concentration gradient between cellular membranes. High concentration can cause non-specific labeling, thus increasing background signals. High concentrations can increase cellular toxicity. Small compounds for in vivo delivery and labeling display extremely poor efficiency due to poor pharmacokinetic properties.
Semiconducting conjugated polymer nanoparticles (CPNs) are emerging fluorescent biomaterials that have been employed for labelling, sensing, and delivery of biological substances. Owing to their fluorescent and lipophilic nature, CPNs are a unique mitochondrial delivery platform that can facilitate understanding of how chemical structures affect the uptake behavior of these polymeric vehicles. CPNs as mitochondrial delivery vehicles are presently limited to formulations with liposomal vehicles.
Polymeric nanoparticles (NPs) can overcome many limitations of concentration and in vivo properties of small molecules. NPs permit various endocytosis pathways to enter cells, and relatively small quantity can be used for labeling of target cells with no need for a concentration gradient. Since NPs are brighter than a typical single fluorescent molecule, high local fluorescent intensities are possible from NPs. However, NPs are very inefficient for labeling of intracellular molecules and organelles because of their high molecular weight.
Hence it is desirable to combine small molecule and NP intracellular targeting advantages. Hence it is desirable to synthesize biodegradable conjugated polymer nanoparticles (CPNs) that can be taken up by cells as NPs and degraded into small fluorescent molecules that label target intracellular organelles.
PPE polymers can be tailored to a specific application through the modulation of their physical, biological and optical properties by structural modifications of the rigid conjugated backbone and the pendant side-chains. More specifically, it would be advantageous if controlled introduction of flexibility into the CP backbone could be carried out with the retention of the optical properties of the fully conjugated PPE polymer while improving the material's solubility, modulating its aggregation properties, or including a biodegradable component for intercellular applications. A flexible content could translate to the formation of segments of shorter conjugation length, and the precise control of the amount of flexibility provides a means to control the length of conjugated segments within a polymer chain. Such a backbone structure could modify complexation with polyanions, and dramatically impact cellular uptake and subcellular localization of conjugated polymer nanoparticles (CPNs). It has not been possible to control the amount of flexible component in PPEs due to the nature of the catalytic system (Glaser coupling).